Dataset Information

Resveratrol improves high-fat diet-induced insulin resistance in mice by downregulating the lncRNA NONMMUT008655.2.

ABSTRACT: As essential players in the field of diabetes treatment, resveratrol (RSV) has received much attention in recent years. However, it is unclear whether it can improve insulin resistance by regulating the long-chain non-coding RNA (lncRNA). The objective of this study was to investigate whether RSV improves high-fat diet-induced insulin resistance in mice by regulating thelncRNANONMMUT008655.2 in vivo and in vitro. To this end, animal and cell insulin resistance models were developed. Specifically, C57BL/6J mice were fed a high-fat diet (HFD) and administered RSV for eight weeks. Additionally, mouse Hepa cells were treated with palmitic acid, transfected with siRNA NONMMUT008655.2, and treated with RSV. Treated mice and cells were then compared to normal controls that were not exposed to RSV. In the animal model, RSV was found to decrease the levels of fasting blood glucose, triglycerides, and low-density lipoprotein cholesterol, as well as the insulin index and area under the curve; while increasing the insulin sensitivity index. Besides, RSV decreased the expression levels of SOCS3, G6PC, and FOXO1 yet increased that of p-Akt and p-FOXO1 in mice. The same results were observed following knockdown of NONMMUT008655.2 in cells. Overall, our results suggest that RSV may improve hepatic insulin resistance and control blood glucose levels by downregulating lncRNA NONMMUT008655.2.

SUBMITTER: Shu L

PROVIDER: S-EPMC7013227 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Resveratrol improves high-fat diet-induced insulin resistance in mice by downregulating the lncRNA NONMMUT008655.2.

Shu Linyi L Hou Guangsen G Zhao Hang H Huang Wenli W Song Guangyao G Ma Huijuan H

American journal of translational research 20200115 1

As essential players in the field of diabetes treatment, resveratrol (RSV) has received much attention in recent years. However, it is unclear whether it can improve insulin resistance by regulating the long-chain non-coding RNA (lncRNA). The objective of this study was to investigate whether RSV improves high-fat diet-induced insulin resistance in mice by regulating thelncRNANONMMUT008655.2 <i>in vivo</i> and <i>in vitro</i>. To this end, animal and cell insulin resistance models were developed ...[more]

PMID: 32051733

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Project description:Recent discovery reveals HFD insult can cause insulin resistance very rapidly, but the underlying mechanism is still not well understood. We performed a short term experiment in a Diet Induced Insulin resistance mouse model. Objective: Insulin resistance (IR) is one of the earliest predictors of type 2 diabetes. However, diagnosis of IR is limited. High fat fed mouse models provide key insights into IR. We hypothesized that early features of IR are associated with persistent changes in gene expression (GE) and endeavoured to (a) develop novel methods for improving signal:noise in analysis of human GE using mouse models; (b) identify a GE motif that accurately diagnoses IR in humans; and (c) identify novel biology associated with IR in humans. Methods: We integrated human muscle GE data with longitudinal mouse GE data and developed an unbiased three-level cross-species analysis platform (single-gene, gene-set and networks) to generate a gene expression motif (GEM) indicative of IR. A logistic regression classification model validated GEM in 3 independent human datasets (n =115). Results: This GEM of 93 genes substantially improved diagnosis of IR compared to routine clinical measures across multiple independent datasets. Individuals misclassified by GEM possessed other metabolic features raising the possibility that they represent a separate metabolic subclass. The GEM was enriched in pathways previously implicated in insulin action and revealed novel associations between Î²-catenin and Jak1 and IR. Functional analyses using small molecule inhibitors showed an important role for these proteins in insulin action. Conclusions: This study shows that systems approaches for identifying molecular signatures provides a powerful way to stratify individuals into discrete metabolic groups. Moreover, we speculate that the Î²-catenin pathway may represent a novel biomarker for IR in humans that warrant future investigation. Comparison of gene expression in muscle tissue during High Fat Diet (HFD) time course (day 5 and day 42). Chow diet will serve as control for HFD. 4 samples per group serve as experimental replicates.

Dataset Information

Resveratrol improves high-fat diet-induced insulin resistance in mice by downregulating the lncRNA NONMMUT008655.2.

Publications

Resveratrol improves high-fat diet-induced insulin resistance in mice by downregulating the lncRNA NONMMUT008655.2.

Similar Datasets

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